Tubulin polymerization-IN-14

Tubulin polymerization-IN-14 (Compound 20a) is a tubulin polymerization inhibitor with an IC50 of 3.15 μM. Tubulin polymerization-IN-14 shows potent anti-vascular and anticancer activities, induces cancer cell apoptosis[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

IC50: 3.15 μM (tubulin polymerization)[1]

Tubulin polymerization-IN-14 (Compound 20a) binds to the colchicine binding site on tubulin[1]. Tubulin polymerization-IN-14 (0-1 μM; 72 h) inhibits cancer cell growth[1]. Tubulin polymerization-IN-14 (5-20 nM; 48 h) arrests K562 cell cycle at G2/M phase, significantly induces cell apoptosis in K562 cells in a concentration-dependent manner, and induces mitochondrial membrane potential (MMP) collapse and mitochondrial dysfunction in K562 cells[1]. Tubulin polymerization-IN-14 (5-20 nM; 24 h) significantly decreases wound closure and capillary-like tubules formation in a concentration-dependent manner in HUVECs[1]. Cell Proliferation Assay[1] Cell Line: K562 cells Concentration: 0-1 μM Incubation Time: 72 h Result: Showed anti-proliferative activity with an IC50 of 0.01 ± 0.001 μM against K562 cells. Cell Cytotoxicity Assay[1] Cell Line: HepG2, HCT-8, MDA-MB-231 and HFL-1 cells Concentration: 0-1 μM Incubation Time: 72 h Result: Showed cytotoxic activities with IC50s of 0.019 ± 0.002, 0.021 ± 0.003, 0.02 ± 0.001 and 0.118 ± 0.007 μM against HepG2, HCT-8, MDA-MB-231 and HFL-1 cells, respectively. Cell Cycle Analysis[1] Cell Line: K562 cells Concentration: 5 nM, 10 nM and 20 nM Incubation Time: 48 h Result: 9.40%, 11.54% and 15.28% of cells were arrested at G2/M phase at 5, 10 and 20 nM, respectively. Apoptosis Analysis[1] Cell Line: K562 cells Concentration: 5 nM, 10 nM and 20 nM Incubation Time: 48 h Result: Compared to the percentage of apoptosis cells in control group (3.25%), the total percentage of the early (Annexin-Vþ/PI) and late (Annexin-Vþ/PIþ) apoptosis cells were 10.46%, 48.55% and 62.26% after being treated at 5, 10, and 20 nM for 48 h, respectively. Cell Migration Assay [1] Cell Line: HUVECs Concentration: 5 nM, 10 nM and 20 nM Incubation Time: 24 h Result: After exposed to compound at 5, 10, and 20 nM for 24 h, cells migrated into 67.6%, 55.3% and 49.2% of the wound area, respectively.

Tubulin polymerization-IN-14 (Compound 20a) (15 and 30 mg/kg; i.v.; daily for 21 days) displays obvious and dose-dependent antitumor effect with no significant toxicity in the liver tumor allograft mouse model[1]. Animal Model: Five-week-old male ICR mice, liver tumor allograft model[1] Dosage: 15 and 30 mg/kg Administration: Intravenous injection, daily for 21 days Result: The decrease in tumor weight reached 68.7% at doses of 30 mg/kg per day at 21 daysafter initiation of treatment as compared to vehicle without obvious loss of body weight.

[1]. Shuai W, et al. Design, synthesis and anticancer properties of isocombretapyridines as potent colchicine binding site inhibitors. Eur J Med Chem. 2020 Jul 1;197:112308.